Drs. Adinoff and Schuster Reply

To the Editor: We appreciate the clinical insights of Dr. Modesto-Lowe regarding the potential dangers of divided methadone dosing. As noted in the editorial, split dosing should not be taken lightly. Patients should be carefully assessed prior to initiating divided dosing. Evidence of withdrawal, including craving, should initially be treated with an increase in daily dosing. If further methadone increases produce clinically unacceptable side effects (i.e., sedation or impairment in performance that prevents safe driving or working) and a working rapport has been established between the patient and physician, then divided dosing should be considered. Patients should first be assessed for rapid methadone metabolism as a result of enzymatic variants, concomitant medications, and/or pregnancy. Prior to implementation, patients should be informed that split dosing will be maintained only if urine drug toxicology screens are negative and withdrawal symptoms abate, the latter offering presumptive evidence that the divided dose is being consumed and is therapeutically appropriate. Questionnaires such as the Opiate Dosage Adequacy Scale can be useful (1) .

Nevertheless, some concerns may be overstated. The excellent review article (2) Dr. Modesto-Lowe references noted that the recent increase in police methadone seizures in the United States has been for tablets dispensed for pain management, not the liquid used for methadone maintenance treatment. Further, the Center for Substance Abuse Treatment (3) documents the following:

The increase in methadone prescription practices appears to be a combination of increasing recognition of the importance of adequate pain relief coupled with concerns over the use of Oxycontin, resulting in a switch to methadone.

Dr. Modesto-Lowe’s concern that the judicious and occasional use of divided methadone dosing may lead to methadone-maintained craving-free individuals “nodding off, robbing banks, and using cocaine and benzodiazepines” evokes memories of “reefer madness” and has little support from empirical evidence. Patients who are sedated should not be provided divided dosing, appropriately medicated patients on opioid agonist therapy experience a dramatic decrease in crime, and most studies indicate a decrease, not an increase, in nonopioid drug use among methadone-maintained individuals.